ACL microtrauma: healing through nutrition, modified sports training, and increased recovery time

Journal of Experimental Orthopaedics - Tập 9 - Trang 1-12 - 2022
J. Nyland1,2,3, B. Pyle2, R. Krupp1,3, G. Kittle2, J. Richards3, J. Brey1,3
1Norton Orthopedic Institute, Louisville, USA
2MSAT Program, Spalding University, Louisville, USA
3Department of Orthopaedic Surgery, University of Louisville, Louisville, USA

Tóm tắt

Sports injuries among youth and adolescent athletes are a growing concern, particularly at the knee. Based on our current understanding of microtrauma and anterior cruciate ligament (ACL) healing characteristics, this clinical commentary describes a comprehensive plan to better manage ACL microtrauma and mitigate the likelihood of progression to a non-contact macrotraumatic ACL rupture. Medical literature related to non-contact ACL injuries among youth and adolescent athletes, collagen and ACL extracellular matrix metabolism, ACL microtrauma and sudden failure, and concerns related to current sports training were reviewed and synthesized into a comprehensive intervention plan. With consideration for biopsychosocial model health factors, proper nutrition and modified sports training with increased recovery time, a comprehensive primary ACL injury prevention plan is described for the purpose of better managing ACL microtrauma, thereby reducing the incidence of non-contact macrotraumatic ACL rupture among youth and adolescent athletes. Preventing non-contact ACL injuries may require greater consideration for reducing accumulated ACL microtrauma. Proper nutrition including glycine-rich collagen peptides, or gelatin-vitamin C supplementation in combination with healthy sleep, and adjusted sports training periodization with increased recovery time may improve ACL extracellular matrix collagen deposition homeostasis, decreasing sudden non-contact ACL rupture incidence likelihood in youth and adolescent athletes. Successful implementation will require compliance from athletes, parents, coaches, the sports medicine healthcare team, and event organizers. Studies are needed to confirm the efficacy of these concepts. V

Tài liệu tham khảo

Abedin M, King N (2010) Diverse evolutionary paths to cell adhesion. Trends Cell Biol 20:734–742. https://doi.org/10.1016/2Fj.tcb.2010.08.002 Ackermann TW (2013) Neuronal regulation of tendon homeostasis. Int J Exp Pathol 94:271–286. https://doi.org/10.1111/iep.12028 Ambrosi D, Ben Amar M, Cyron CJ, DeSimone A, Goriely A, Humphrey JD, Kuhl E (2019) Growth and remodeling of living tissues: perspectives, challenges and opportunities. J R Soc Interface 16:20190233. https://doi.org/10.1098/rsif.2019.0233 Anoka N, Nyland J, McGinnis M, Lee D, Doral MN, Caborn DNM (2012) Consideration of growth factors and bio-scaffolds for treatment of combined grade II MCL and ACL injury. Knee Surg Sports Traumatol Arthrosc 20:878–888. https://doi.org/10.1007/s00167-011-1641-7 Arnoczky SP (1983) Anatomy of the anterior cruciate ligament. Clin Orthop Relat Res 172:19–25 PMID: 6821989 Atarod M, Frank CB, Shrive NG (2014) Decreased posterior cruciate and altered collateral ligament loading following ACL transection: a longitudinal study in the ovine model. J Orthop Res 32:431–438. https://doi.org/10.1002/jor.22529 Avanzion L, Pelosin E, Abbruzzese G, Bassolino M, Pozzo T, Bove M (2014) Shaping motor cortex plasticity through proprioception. Cereb Cortex 24:2807–2814. https://doi.org/10.1093/cercor/bht139 Baar K (2017) Minimizing injury and maximizing return to play: lessons from engineered ligaments. Sports Med 47(Suppl 1):S5–S11. https://doi.org/10.1007/s40279-017-0719-x Beaulieu ML, Carey GE, Schlecht SH et al (2016) On the heterogeneity of the femoral enthesis of the human ACL: microscopic anatomy and clinical implications. J Exp Orthop 3:14. https://doi.org/10.1186/s40634-016-0050-8 Bedi A, Warren RF, Wojtys EM et al (2016) Restriction in hip internal rotation is associated with an increased risk of ACL injury. Knee Surg Sports Traumatol Arthrosc 24:2024–2031. https://doi.org/10.1007/s00167-014-3299-4 Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR (2002) The skeletal attachment of tendons – tendon “entheses”. Comp Biochem Physiol A Mol Integr Physiol 133:931–945. https://doi.org/10.1016/s1095-6433(02)00138-1 Birch HL, Thorpe CT, Rumian AP (2013) Specialisation of extracellular matrix for function in tendons and ligaments. MLTJ 3:12–22. https://doi.org/10.11138/mltj/2013.3.1.012 Boden BP, Dean GS, Feagin JA, Garrett WE (2000) Mechanisms of anterior cruciate ligament injury. Orthop 23:573–580. https://doi.org/10.3928/0147-7447-20000601-15 Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15:786–801. https://doi.org/10.1038/nrm3904 Boys AJ, McCorry RS, Rodeo S, Bonassar LJ, Estroff LA (2017) Next generation tissue engineering of orthopedic soft tissue-to-bone interfaces. MRS Commun 7:289–308. https://doi.org/10.1557/mrc.2017.91 Brown MN, Shiple BJ, Scarpone M (2016) Regenerative approaches to tendon and ligament conditions. Phys Med Rehabil Clin N Am 27:941–984. https://doi.org/10.1016/j.pmr.2016.07.003 Burke L, Deakin V (2015) Clinical sports nutrition, 5th edn. McGraw-Hill, Australia, Sydney ISBN: 9781743073681 Burr DB, Robling AG, Turner CH (2002) Effects of biomechanical stress on bones in animals. Bone 30:781–786. https://doi.org/10.1016/s8756-3282(02)00707-x Chang J, Garva R, Pickard A, Yeung CC, Mallikarjun V, Swift J, Holmes DF, Calverley B, Lu Y, Adamson A, Raymond-Hayling H, Jensen O, Shearer T, Meng QJ, Kadler KE (2020) Circadian control of the secretory pathway maintains collagen homeostasis. Nat Cell Biol 22:74–86. https://doi.org/10.1038/s41556-019-0441-z Chanrashekar N, Mansouri H, Slauterbeck J, Hashemi J (2006) Sex-based differences in the tensile properties of the human anterior cruciate ligament. J Biomech 39:2943–2950. https://doi.org/10.1016/j.jbiomech.2005.10.031 Chaudhari AM, Zelman EZ, Flanigan DC, Kaeding CC, Nagaraja HN (2009) Anterior cruciate ligament- injured subjects have smaller anterior cruciate ligaments than matched controls: a magnetic resonance imaging study. Am J Sports Med 37:1282–1287. https://doi.org/10.1177/0363546509332256 Chen J, Kim J, Shao W, Schlecht SH, Baek SY, Jones AK, Ahn T, Ashton-Miller JA, Banaszak Holl MM, Wojtys EM (2019) An anterior cruciate ligament failure mechanism. Am J Sports Med 47:2067–2076. https://doi.org/10.1177/0363546519854450 Chow JW, Chambers TJ (1994) Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am J Phys 267(2 pt 1):E287–E292. https://doi.org/10.1152/ajpendo.1994.267.2.E287 Christensen B, Dandanell S, Kjaer M, Langberg H (2011) Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans. J Appl Physiol 110:137–141. https://doi.org/10.1152/japplphysiol.00942.2010 Clark D, Schumann F, Mostofsky SH (2015) Mindful movement and skilled attention. Front Hum Neurosci 9:297. https://doi.org/10.3389/fnhum.2015.00297 Clark K, Langeslag M, Figdor CG, van Leeuwen FN (2007) Myosin II and mechanotransduction: a balancing act. Trends Cell Biol 17:178–186. https://doi.org/10.1016/j.tcb.2007.02.002 Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A (2008) 24-week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin 24:1485–1496. https://doi.org/10.1185/030079908X291967 Close GL, Sale C, Baar K, Bermon S (2019) Nutrition for the prevention and treatment of injuries in track and field athletes. Int J Sport Nutr Exerc Metab 29:189–197. https://doi.org/10.1123/ijsnem.2018-0290 Cottrell JA, Turner JC, Arinzeh TL, O’Connor JP (2016) The biology of bone and ligament healing. Foot Ankle Clin N Am 21:739–761. https://doi.org/10.1016/j.fcl.2016.07.017 Couppe C, Kongsgaard M, Aagaard P, Hansen P, Bojsen-Moller J, Kjaer M, Magnusson SP (2008) Habitual loading results in tendon hypertrophy and increased stiffness of the human patellar tendon. J Appl Physiol 105:805–810. https://doi.org/10.1152/japplphysiol.90361.2008 Crane JD, MacNeil LG, Lally IS, Ford RJ, Bujak AL, Brar IK, Kemp BE, Raha S, Steinberg GR, Tarnopolsky MA (2015) Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging. Aging Cell 14:625–634. https://doi.org/10.1111/acel.12341 Cyron CJ, Humphrey JD (2017) Growth and remodeling of load-bearing biological soft tissues. Meccanica 52:645–664. https://doi.org/10.1007/s11012-016-0472-5 Derwin KA, Galatz LM, Ratcliffe A, Thomopoulos S (2018) Enthesis repair: challenges and opportunities for effective tendon-to-bone healing. J Bone Joint Surg Am 100:1–7. https://doi.org/10.2106/2FJBJS.18.00200 Dodt C, Breckling U, Derad I, Fehm HL, Born J (1997) Plasma epinephrine and norepinephrine concentrations of healthy humans associated with nighttime sleep and morning arousal. Hypertension 30:71–76. https://doi.org/10.1161/01.hyp.30.1.71 Glatt V, Evans CH, Stoddart MJ (2019) Regenerative rehabilitation: the role of mechanotransduction in orthopaedic regenerative medicine. J Orthop Res 37:1263–1269. https://doi.org/10.1002/jor.24205 Goddard M, Bowman N, Salmon LJ, Walker A, Roe JP et al (2013) Endoscopic anterior cruciate ligament reconstruction in children using living donor hamstring tendon allografts. Am J Sports Med 41:567–574. https://doi.org/10.1177/0363546512473576 Gottschalk AW, Andrish JT (2011) Epidemiology of sports injury in pediatric athletes. Sports Med Arthrosc Rev 19:2–6. https://doi.org/10.1097/jsa.0b013e31820b95fc Guo Z, De Vita R (2009) Probabilistic constitutive law for damage in ligaments. Med Eng Phys 31:1104–1109. https://doi.org/10.1016/j.medengphy.2009.06.011 Heinemeier KM, Olesen JL, Haddad F et al (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582(Pt 3):1303–1316. https://doi.org/10.1113/jphysiol.2007.127639 Heinemeier KM, Olesen JL, Haddad F, Schjerling P, Baldwin KM, Kjaer M (2009) Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle. J Appl Physiol 106:178–186. https://doi.org/10.1152/japplphysiol.91092.2008 Hoppeler H, Baum O, Lurman G, Mueller M (2011) Molecular mechanisms of muscle plasticity and exercise. Compr Physiol 1:1383–1412. https://doi.org/10.1002/cphy.c100042 Humphrey JD, Dufresne ER, Schwartz MS (2014) Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 15:802–812. https://doi.org/10.1038/nrm3896 Issurin VB (2010) New horizons for the methodology and physiology of training periodization. Sports Med 40:189–206. https://doi.org/10.2165/11319770-000000000-00000 Ivarsson A, Johnson U, Andersen MB, Tranaeus U, Stenling A, Lindwall M (2016) Psychosocial factors and sport injuries: meta analyses for prediction and prevention. Sports Med 47:353–365. https://doi.org/10.1007/s40279-016-0578-x Jung HJ, Fisher MB, Woo SL (2009) Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons. Sports Med Arthrosc Rehabil Ther Technol 1:9. https://doi.org/10.1186/1758-2555-1-9 Kennedy JC, Hawkins RJ, Willis RB, Danylchuk KD (1976) Tension studies of human knee ligaments. Yield point, ultimate failure, and disruption of the cruciate and tibial collateral ligaments. J Bone Joint Surg Am 58:350–355 PMID: 1262366 Kiely J (2017) The robust running ape: unraveling the deep underpinnings of coordinated human running proficiency. Front Psychol 8:892. https://doi.org/10.3389/fpsyg.2017.00892 Kiely J (2018) Periodization training: confronting an inconvenient truth. Sports Med 48:753–764. https://doi.org/10.1007/s40279-017-0823-y Kiely J, Collins DJ (2016) Uniqueness of human running coordination: the integration of modern and ancient evolutionary innovations. Front Psychol 7:262. https://doi.org/10.3389/fpsyg.2016.00262 Kjaer M, Langberg H, Heinemeier K, Bayer ML, Hansen M, Holm L, Doessing S, Kongsgaard M, Krogsgaard MR, Magnusson SP (2009) From mechanical loading to collagen synthesis, structural changes and function in human tendon. Scand J Med Sci Sports 19:500–510. https://doi.org/10.1111/j.1600-0838.2009.00986.x Kohrt WM, Barry DW, Van Pelt RE et al (2010) Timing of ibuprofen use and bone mineral density adaptations to exercise training. J Bone Miner Res 25:1415–1422. https://doi.org/10.1002/jbmr.24 Kruger A (2016) From Russia with love? Sixty years of proliferation of L.P. Matveyev’s concept of periodization? Staps 114:51–59 ISSN 0247-106X Langberg H, Skovgaard D, Petersen LJ, Bulow J, Kjaer M (1999) Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans. J Physiol 521 Pt 1(Pt 1):299–306. https://doi.org/10.1111/j.1469-7793.1999.00299.x Laxdal G, Kartus J, Ejerhed I et al (2005) Outcome and risk factors after anterior cruciate ligament reconstruction: a follow-up study of 948 patients. Arthroscopy 21:958–964. https://doi.org/10.1016/j.arthro.2005.05.007 Leadbetter WB (1992) Cell-matrix response in tendon injury. Clin Sports Med 11:533–578 PMID: 1638640 Lipps DB, Wojtys EM, Ashton-Miller JA (2013) Anterior cruciate ligament fatigue failures in knees subjected to repeated simulated pivot landings. Am J Sports Med 41:1058–1066. https://doi.org/10.1177/0363546513477836 Liu PPY, Zhang P, Chang K-M, Qin L (2010) Biology and augmentation of tendon-bone insertion repair. J Orthop Surg Res 5:59. https://doi.org/10.1186/1749-799x-5-59 Louw Q, Manilall J, Grimmer K (2008) Epidemiology of knee injuries among adolescents: a systematic review. Br J Sports Med 42:2–10. https://doi.org/10.1136/bjsm.2007.035360 McAlindon TE, Nuite M, Krishnan N, Rudhazer R, Price LL, Burstein D, Griffith J, Flechsenhar K (2011) Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthr Cart 19:399–405. https://doi.org/10.1016/j.joca.2011.01.001 Meeuwisse WH (2009) What is the mechanism of no injury (MONI)? Clin J Sport Med 19:1–2. https://doi.org/10.1097/jsm.0b013e3181979c1d Merkel DL (2013) Youth sport: positive and negative impact on young athletes. Open Access J Sports Med 4:151–160. https://doi.org/10.2147/oajsm.s33556 Moshiri A, Oryan A (2013) Tendon and ligament tissue engineering, healing and regenerative medicine. J Sports Med Doping Stud 3:126. https://doi.org/10.4172/2161-0673.1000126 Murray MM, Martin SD, Martin TL, Spector M (2000) Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg Am 82:1387–1397. https://doi.org/10.2106/00004623-200010000-00004 Nielsen R, Akey JM, Jakobsson M, Pritchard JK, Tishkoff S, Willerslev E (2017) Tracing the peopling of the world through genomics. Nature 541:302–310. https://doi.org/10.1038/nature21347 Novaretti JV, Astur DC, Casadio D, Nicolini AP, de Castro PA, Andreoli CV, Ejnisman B, Cohen M (2018) Higher gene expression of healing factors in anterior cruciate ligament remnant in acute anterior cruciate ligament tear. Am J Sports Med 46:1583–1591. https://doi.org/10.1177/0363546518760577 Noyes FR, DeLucas JL, Torvik PJ (1974) Biomechanics of anterior cruciate ligament failure: an analysis of strain-rate sensitivity and mechanisms of failure in primates. J Bone Joint Surg Am 56(2):236–253 PMID: 4452684 Nyland J, Gamble C, Franklin T, Caborn DNM (2017) Permanent knee sensorimotor system changes following ACL injury and surgery. Knee Surg Sports Traumatol Arthrosc 25:1461–1474. https://doi.org/10.1007/s00167-017-4432-y Nyland J, Huffstutler A, Faridi J et al (2020) Cruciate ligament healing and injury prevention in the age of regenerative medicine and technostress: homeostasis revisited. Knee Surg Sports Traumatol Arthrosc 28:777–789. https://doi.org/10.1007/s00167-019-05458-7 Nyland J, Moatshe G, Martin R (2022) Combined ACL and anterolateral ligament reconstruction: time to pivot and shift the focus? Knee Surg Sports Traumatol Arthrosc https://doi.org/10.1007/s00167-022-07072-667 Nyland J, Pyle B (2022) Self-identity and adolescent return to sports post-ACL injury and rehabilitation: will anyone listen? ASMAR 4:e287–e294. https://doi.org/10.1016/j.asmr.2021.09.042 Oh YK, Lipps DB, Ashton-Miller JA, Wojtys EM (2012) What strains the anterior cruciate ligament during a pivot landing? Am J Sports Med 40:574–583. https://doi.org/10.1177/0363546511432544 Panjabi MM (2006) A hypothesis of chronic back pain: ligament subfailure injuries lead to muscle control dysfunction. Eur Spine J 15:668–676. https://doi.org/10.1007/s00586-005-0925-3 Panjabi MM, Courtney W (2001) High-speed subfailure stretch of rabbit anterior cruciate ligament: changes in elastic, failure and viscoelastic characteristics. Clin Biomech 16:334–340. https://doi.org/10.1016/s0268-0033(01)00007-9 Panjabi MM, Yoldas E, Oxland TR, Crisco JJ (1996) Subfailure injury of the rabbit anterior cruciate ligament. J Orthop Res 14:216–222. https://doi.org/10.1002/jor.1100140208 Paxton JZ, Grover LM, Baar K (2016) Engineering an in vivo model of a functional ligament from bone to bone. Tissue Eng Part A 16:3515–3525. https://doi.org/10.1089/ten.tea.2010.0039 Paxton JZ, Hagerty P, Andrick JJ et al (2012) Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments. Tissue Eng Part A 18:277–284. https://doi.org/10.1089/ten.tea.2011.0336 Perez-Castro AV, Vogel KG (1999) In situ expression of collagen and proteoglycan during development of fibrocartilage in bovine deep flexor tendons. J Orthop Res 17:139–148. https://doi.org/10.1002/jor.1100170120 Petrofsky JS, Khowailed IA, Lee H, Berk L, Bains GS, Akerkar S, Al-Dabbak F, Laymon MS (2015) Cold vs. heat after exercise-is there a clear winner for muscle soreness. J Strength Cond Res 29:3245–3252. https://doi.org/10.1519/jsc.0000000000001127 Pioletti DP, Rakotomanana LR (2000) On the independence of time and strain effects in the stress relaxation of ligaments and tendons. J Biomech 33:1729–1732. https://doi.org/10.1016/s0021-9290(00)00128-7 Provenzano PP, Heisey D, Hayashi K, Lakes R, Vandeby R Jr (2002) Subfailure damage in ligament: a structural and cellular evaluation. J Appl Physiol 92:362–371. https://doi.org/10.1152/jappl.2002.92.1.362 Robi K, Jakob N, Matevz K, Matjaz V (2013) The physiology of sports injuries and repair processes, chapter 2. In: Hamlin M, Draper N, Kathiravel Y (eds) Current issues in sports and exercise medicine. IntechOpen, London, pp 43–86. https://doi.org/10.5772/54234 Roos KG, Marshall SW, Kerr ZY, Golightly YM, Kucera KL, Myers JB, Rosamond WD, Comstock RD (2015) Epidemiology of overuse injuries in collegiate and high school athletics in the United States. Am J Sports Med 43:1790–1797. https://doi.org/10.1177/0363546515580790 Salzmann GM, Niemeyer P, Hochrein A, Stoddart MJ, Angele P (2018) Articular cartilage repair of the knee in children and adolescents. Orthop J Sports Med 6:2325967118760190. https://doi.org/10.1177/2325967118760190 Sauterbeck JR, Hickox JR, Beynnon B, Hardy DM (2006) Anterior cruciate ligament biology and its relationship to injury forces. Orthop Clin N Am 37:585–591. https://doi.org/10.1016/j.ocl.2006.09.001 Schulze-Tanzil G (2019) Intraarticular ligament degeneration is interrelated with cartilage and bone destruction in osteoarthritis. Cells 8:990. https://doi.org/10.3390/cells8090990 Screen HR, Shelton JC, Bader DL, Lee DA (2005) Cyclic tensile strain upregulates collagen synthesis in isolated tendon fascicles. Biochem Biophys Res Commun 336:424–429. https://doi.org/10.1016/j.bbrc.2005.08.102 Sensini A, Massafra G, Gotti C, Zucchelli A, Cristofolini L (2021) Tissue engineering for the insertions of tendons and ligaments: an overview of electrospun biomaterials and structures. Front Bioeng Biotechnol 9:645544. https://doi.org/10.3389/2Ffbioe.2021.645544 Shaw G, Lee-Barthel A, Ross MLR, Wang G, Baar K (2017) Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr 105:136–143. https://doi.org/10.3945/ajcn.116.138594 Sherwood A, Johnson K, Blumenthal JA, Hinderliter AL (1999) Endothelial function and hemodynamic responses during mental stress. Psychosom Med 61:365–370. https://doi.org/10.1097/00006842-199905000-00017 Shriner D, Tekola-Ayele F, Adeyemo A, Rotimi CN (2016) Ancient human migration after out-of- Africa. Sci Rep 6:26565. https://doi.org/10.1038/srep26565 Spindler KP, Murray MM, Devin C, Nanney LB, Davidson LM (2006) The central ACL defect as a model for failure of intra-articular healing. J Orthop Res 24:401–406. https://doi.org/10.1002/jor.20074 Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK (2016) Extracellular matrix structure. Adv Drug Deliv Rev 97:4–27. https://doi.org/10.1016/j.addr.2015.11.001 Thijssen DH, Carter SE, Green DJ (2016) Arterial structure and function in vascular ageing: are you as old as your arteries? J Physiol 594(8):2275–2284. https://doi.org/10.1113/jp270597 Thompson WR, Scott A, Loghmani MT, Ward SR, Warden SJ (2018) Understanding mechanobiology: physical therapists as a force in mechanotherapy and musculoskeletal regenerative rehabilitation. Phys Ther 96:560–569. https://doi.org/10.2522/ptj.20150224 Thornton GM, Schwab TD, Oxland TR (2017) Cyclic loading causes faster rupture and strain rate than static loading in medial collateral ligament at high stress. Clin Biomech (Bristol, Avon) 22:932–940. https://doi.org/10.1016/j.clinbiomech.2007.05.004 Toy BJ, Yeasting RA, Morse DE, McCann P (1995) Arterial supply to the human anterior cruciate ligament. J Athl Train 30:149–152 PMCID: PMC1317848 Tricker R (2000) Painkilling drugs in collegiate athletics: knowledge, attitudes, and use of student athletes. J Drug Educ 30:313–324. https://doi.org/10.2190/n1k3-v8bk-90gh-tthu Tscholl P, Junge A, Dvorak J (2008) The use of medication and nutritional supplements during FIFA world cups 2002 and 2006. Br J Sports Med 42:725–730. https://doi.org/10.1136/bjsm.2007.045187 Turnagol HH, Kosar SN, Guzel Y, Aktitiz S, Atakan MM (2022) Nutritional considerations for injury prevention and recovery in combat sports. Nutrients 14:53. https://doi.org/10.3390/nu14010053 van der Worp MP, Ten Haaf DS, van Cingel R, de Wijer A, Nihjuis-van der Sanden MW, Staal JB (2015) Injuries in runners: a systematic review on risk factors and sex differences. PLoS One 10:e0114927. https://doi.org/10.1371/journal.pone.0114937 Waddington I, Malcolm D, Roderick M et al (2005) Drug use in English professional football. Br J Sports Med 39:e18. https://doi.org/10.1136/bjsm.2004.012468 West DWD, Lee-Barthel A, McIntyre T, Shamim B, Lee CA, Baar K (2015) The exercise-induced biochemical milieu enhances collagen content and tensile strength in engineered ligaments. J Physiol 593:4665–4675. https://doi.org/10.1113/jp270737 Wiese-Bjornstal DM (2010) Psychology and socioculture affect injury risk, response, and recovery in high-intensity athletes: a consensus statement. Scand J Med Sci Sports 20(suppl 2):103–111. https://doi.org/10.1111/j.1600-0838.2010.01195.x Wojtys E, Beaulieu ML, Ashton-Miller JA (2016) New perspectives on ACL injury: on the role of repetitive sub-maximal knee loading in causing ACL fatigue failure. J Orthop Res 34:2059–2068. https://doi.org/10.1002/jor.23441 Woo SL, Debski RE, Zeminski J, Abramowitch SD, Swa SS, Fenwick JA (2000) Injury and repair of ligaments and tendons. Annu Med Biomed Eng 2:83–118. https://doi.org/10.1146/annurev.bioeng.2.1.83 Woo SL, Gomez MA, Sites TJ, Newton PO, Orlando CA, Akeson WH (1987) The biomechanical and morphological changes in the medial collateral ligament of the rabbit after immobilization and remobilization. J Bone Joint Surg Am 69:1200–1211 PMID: 3667649 World Health Organization (2001) ICF: international classification of functioning, disability and health. World Health Organization, Geneva ISBN 92 4 154542 9 Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, Xie L, Jin K (2017) Age-related impairment of vascular structure and functions. Aging Dis 8:590–610. https://doi.org/10.14336/ad.2017.0430101 Yang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99:203–222. https://doi.org/10.1002/bdrc.21041 Young K, Samiric T, Feller J, Cook J (2011) Extracellular matrix content of ruptured anterior cruciate ligament tissue. Knee 18:242–246. https://doi.org/10.1016/j.knee.2010.05.008 Zhao L, Thambyah A, Broom N (2015) Crimp morphology in the ovine anterior cruciate ligament. J Anat 226:278–288. https://doi.org/10.1111/joa.12276 Zhao L, Thambyah A, Broom ND (2014) A multi-scale structural study of the porcine anterior cruciate ligament tibial enthesis. J Anat 224:624–633. https://doi.org/10.1111/joa.12174 Zitnay JL, Jung GS, Lin AH, Qin Z, Li Y, Yu SM, Buehler MJ, Weiss JA (2020) Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues. Sci Adv 6:eaba2795. https://doi.org/10.1126/sciadv.aba2795